The occurrence of dramatic changes in mood, behavior, cognition and somatic functioning in some women in relation to the menstrual cycle has recently been the focus of a great deal of public scrutiny. This project is designed to study the psychobiology and treatment response of women with well-defined menstrually-related mood disorders. The longitudinal screening methods developed by this group are capable of distinguishing women with menstrually- related mood syndromes from those who only believe that they have such a syndrome. With these methods, we have identified the following: 1) the occurrence of the characteristic premenstrual ;syndrome state during an antiprogestin-induced follicular phase; 2) a reduction of PMS symptoms during clonidine infusion; 3) menstrual cycle phase-dependent changes in perception of cognitive performance in patients with menstrually-related mood disorders but not controls; 4) a lack of relationship between self- ratings of fatigue and sleep characteristics, but a positive correlation between self-ratings of mood and fatigue; 5) evidence of abnormal basal thyroid measures in 10% of patients with PMS. The goals of this project are to detect and accurately describe menstrually-related mood disorders, explore their pathophysiology and response to pharmacological and environmental manipulation, and to document the relationship between reproductive endocrine change and disorders of mood as a way of further investigating the neurobiology of psychiatric illness.